X-ray mammography is the clinical tool currently used for breast cancer detection. However, mammography is ionizing radiation and has an unacceptable false negative rate for patients with radiodense breast tissues. These patients represent the general population Of premenopausal women as well as those with fibrocystic tissue disease. Yet, cancer in younger women tends to be more virulent and grow faster. Consequently, there is a critical need to seek alternatives that could overcome the problems associated with x-ray mammography and that could become an excellent adjunct or competitive tool to conventional x-ray mammography. Non-ionizing, noninvasive near-infrared optical imaging has great potential to become such a promising alternative for breast cancer detection. In this regard, our recent studies have shown that millimeter size objects embedded in thick turbid media can be imaged using frequency-domain optical measurements. This indicates the possibility of clinical application of this technique in breast cancer detection. However, the rationale of optical imaging is based on only endogenous differences in the absorption and/or scattering properties between the normal and diseased tissues. On the other hand, fluorescence spectroscopy/imaging studies of human tissue suggest that a variety of lesions show distinct fluorescence spectra compared to those of normal tissue. It has been evidenced that fluorescence spectroscopy of endogenous compounds can provide enhanced contrast as well as diagnostic information. It has also been shown that exogenous dyes exhibit selective uptake in neoplastic lesions and may offer the best contrast for optical imaging. Use of exogenous agents would provide fluorescent markers which could serve to detect embedded tumors in the breast. In particular, the ability to monitor the fluorescent yield and lifetime may also enable biochemical specificity if the fluorophore is sensitive to a specific metabolite, such as oxygen, glucose, etc. Consequently, the proposed research is aimed at combining the best aspects of both endogenous optical imaging and exogenous fluorescent lifetime and yield imaging. This may provide the best sensitivity and specificity for diagnosis with optical techniques. Our specific aims in this project include (1) continued development of our computer algorithms needed for generating images, (2) construction and test of a combined optical and fluorescence imaging system using intensity modulated light and tomographic-like excitation and data collection, (3) evaluation and optimization of this system using tissue phantom experiments.